Background: The health of the next generation is likely programmed in the womb (i.e.in utero), and our understanding of how that programming happens will allow us to favorably influence the health of future generations. The focus of this proposal is to examine the effect of in utero programming on heart function in children born to women with type 2 diabetes (T2DM). Specifically, neonates born to diabetic women have abnormal heart structure and weaker heart function at birth, which may predispose them to long-term heart problems in childhood, adolescence and adulthood. At present, the reason for these heart abnormalities in children born to women with diabetes is unknown and is the focus of this proposal.

Objective(s) and Hypothesis(es): The objectives are to examine the relationships among maternal lipid (fatty acid, triglyceride, very low density lipoprotein) metabolism and neonatal heart structure and function in diabetes and to identify clinical markers during pregnancy for heart dysfunction in infants born to diabetic women. The overall hypothesis is that maternal lipid metabolism is abnormal in diabetes, and this metabolic dysregulation increases fatty acid delivery to the fetus in utero and leads to abnormal accumulation of lipid in the fetal heart, resulting in altered neonatal heart structure and function in infants born to diabetic women. In addition, the investigators hypothesize that decreased maternal fatty acid oxidation (fat "burning") rate, elevated lipolytic (fat breakdown) rate and elevated blood total free fatty acid level predicts abnormal neonatal heart structure and function in infants born to women with type 2 diabetes.

Potential Impact: Type 2 diabetes is an epidemic in the United States and is steadily increasing worldwide. Diabetes has detrimental health effects in pregnant women and in their offspring. The investigators know that children born to women with diabetes have an increased risk for developing diabetes, obesity and cardiovascular disease, than children born to healthy women. This proposal will address an important knowledge gap regarding the role of maternal lipid (and potentially other nutrients) metabolism on the cardiovascular health of the global and increasing population of children born to diabetic women. Findings from this project will be novel and innovative, and will likely point to clinical interventions that target and correct lipid and other metabolic abnormalities in women with pre-gestational diabetes. The impact will be great because the long-term goal is to ameliorate heart problems in children born to diabetic (both pre-gestational and gestational) women. In addition, this project will establish a small cohort of children that can be followed long-term to address novel questions about the progression of heart and other metabolic abnormalities in children born to diabetic women.

Women will be diagnosed with type 2 DM (pre-gestational, White classification B or C class). Since the majority of women with B or C class DM are on insulin therapy in our clinic, we will recruit only women on insulin therapy (i.e. no oral diabetes medications).

HbA1C ≤ 8 for greater than 3 months32, 33.

All women will have confirmed singleton pregnancies.

Receive care at the Women's Health Clinic at Barnes Jewish Hospital.

Pre-pregnancy BMI is anticipated to be >30 (i.e. obese) from the data regarding the patient population of our clinic. Women with pre-pregnancy BMI between 23-40 will be included.

Healthy, overweight/obese pregnant controls

No diagnosis of type 1 or 2 diabetes or previous gestational DM.

Women with pre-pregnancy BMI between 23-40: control participants will be BMI matched to women with DM.

Participants: All women who seek pre-natal care at the Women's Health Clinic Barnes Jewish Hospital in St. Louis, Missouri are screened by history at the first visit for a pre-existing diagnosis of diabetes mellitus (DM) (B or C type DM). Patients with a diagnosis of pre-gestational diabetes are transferred to a specialty clinic dedicated specifically to pre-natal care for women with diabetes. All patients with on-going pregnancies and diabetes will be approached for enrollment. Non-DM subjects have a routine screen for gestational diabetes at 24 wk gestation. After a normal result, these subjects will be approached for enrollment as controls.

Criteria

Inclusion Criteria:

Diabetes Mellitus:

Women will be diagnosed with type 2 DM (pre-gestational, White classification B or C class). Since the majority of women with B or C class DM are on insulin therapy in our clinic, the investigators will recruit only women on insulin therapy (i.e. no oral diabetes medications).

HbA1C ≤ 8 for greater than 3 months 32, 33.

All women will have confirmed singleton pregnancies.

Receive care at the Women's Health Clinic at Barnes Jewish Hospital.

Pre-pregnancy BMI is anticipated to be > 30 (i.e. obese) from the data regarding the patient population of our clinic. Women with pre-pregnancy BMI between 23-40 will be included.

Control Participants:

No diagnosis of type 1 or 2 diabetes or previous gestational DM.

Women with pre-pregnancy BMI between 23-40: control participants will be BMI matched to women with DM.

Patients will have a singleton pregnancy with no fetal abnormalities (as determined by routine standard of care ultrasonography).

Exclusion Criteria:

Multiple gestation pregnancy.

Oral diabetes medications.

Inability to provide voluntary informed consent.

Currently using illegal drugs (cocaine, methamphetamine, opiates).

Current smoker who does not agree to stop.

Participants with diabetes who have a BMI > 40.

Participants who participate in a routine (> 1x/week) exercise program.

History of heart disease.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01346527